Updates from IAS

News from the International AIDS Conference

by Jeff Berry

The Sydney Declaration

This year’s conference organizers announced a global sign-on letter, the Sydney Declaration, inviting all stakeholders including clinicians, researchers, policymakers, and those living with HIV, to join together in urging governments and donors to allocate “no less than 10% of all resources dedicated to HIV programming for research.” Individuals can sign on to the declaration at www.iasociety.org.

Dual vs. triple-drug therapy in naives

A study from Italy in 152 treatment-naïve individuals looked at Kaletra (lopinavir/ritonavir) in combination with one or two nucleosides. Around half of the participants received Kaletra plus Viread (tenofovir), and the other half received Kaletra plus two nukes. CD4+ T-cell (T-cell) increases were higher in the dual group (250) than in the group receiving triple-drug therapy (152). A trend toward lower lipid elevations was also seen in the dual group. Viral load reductions were similar in both groups, suggesting a boosted protease inhibitor (PI) regimen may not always require the use of two nucleosides in some individuals.

To boost or not to boost

Two studies which looked at Reyataz (atazanavir) boosted with Norvir (ritonavir) compared to unboosted Reyataz showed similar results to previous findings. 96-week data from one study of 200 treatment-naïve individuals randomized to receive either boosted or unboosted Reyataz plus 3TC and d4T found comparable viral load reductions and T-cell increases in both groups, however there were more virologic failures and more resistance mutations in those failing unboosted Reyataz. No one in the study receiving boosted Reyataz developed phenotypic resistance to it or any PI, suggesting that when you can, it’s better to boost.

Lexiva vs. Reyataz

48-week data from the ALERT study with 106 participants looked at two groups, one using a regimen containing Lexiva (fos-amprenavir) boosted with a lower dose of Norvir (100 mg) compared to another group using boosted Reyataz, both in combination with Truvada (Viread/Emtriva), and found similar efficacy in both groups. There was some reduction in renal function, although about the same in both groups, and lipid changes were also similar. The frequency of grade 2-4 adverse events was higher in the Reyataz group, but this difference was largely explained by elevated levels of unconjugated bilirubin (this is a blood test result that generally has no side effects except possibly some skin darkening). The current recommended boosting dose of Norvir is 200 mg when used with Lexiva. This was a small study in treatment-naïve individuals, and while it may be too soon to tell, it does suggest that at some point it may be possible to use a lower dose of Norvir to boost Lexiva.

Prezista vs. Kaletra

TITAN is a phase 3 study of 595 treatment-experienced individuals comparing boosted Prezista to Kaletra, both in combination with an optimized background regimen (OBR). Based on a primary endpoint of viral load less than 400 at 48 weeks, it showed that Prezista/r was non-inferior to Kaletra. Both Prezista/r and Kaletra were taken at the twice-daily dose. Adverse events were similar in the two groups, with a higher incidence of diarrhea in the Kaletra group. The old gel-capsule formulation of Kaletra was used during the study.

Aging, or AIDS?

Monday’s plenary session included an enlightening presentation on HIV and aging by Brian Gazzard, M.D. of Chelsea Westminster Hospital. One-third of all adults who are HIV-positive in the U.K. are 55 or older, a “quite staggering statistic,” and his talk sought to address the intersecting relationships between aging, HIV, and the effects of highly active antiretroviral therapy (HAART). Gazzard explained that older people tend to have a poor immune response, and the immune response to HAART is reduced in older people. On the other hand, studies have shown that people over 50 tend to better adhere to therapy, with over 95% adherence. Chronic diseases that are usually associated with aging, such as liver failure, chronic liver disease, and loss of bone mineral density, are more common in those with HIV. So there is, in his words, “a changing perception that many of the diseases of old age will kill us, and they will more likely kill us if we’re HIV-positive than if we’re HIV-negative.”

The D:A:D study has shown that after adjusting for NNRTI exposure there is an incrementally increased risk each year of developing cardiovascular disease for those on HAART. But one of the interesting things Gazzard pointed out in his talk was that the relative risk goes down each year, “so the longer you’ve been exposed to these drugs, actually the relative risk seems to be diminishing that you will get cardiovascular disease.” He went on to add that looking at additional findings from the recently halted SMART study, one could surmise that “HIV itself is associated with a very big increase in cardiovascular risk that is reduced enormously by antiretroviral drugs, but not actually completely back to normal. [A] very different idea [from] those that we had before.”

All photos of IAS 2007 Conference courtesy of International AIDS Society

Gazzard pointed out that large numbers of HIV-positive individuals are dying prematurely of cancers that are not necessarily classic cancers that we associate with AIDS, especially the older you get and the lower your T-cell count.

Regarding dementia, although Gazzard says he has not observed it as much in his own practice, he did say that the changes can be more subtle than we realize. HAART itself may actually increase the risk of dementia, while HIV may contribute to Alzheimer’s disease. He ended with the grim prediction that there may be a whole new epidemic of dementia in store for us.

Finishing the talk on a somewhat more upbeat note, Gazzard encouraged those in the audience who were younger to remember how important it is to continue to do research in this area, and that it is a very exciting time. “Please make it simple,” said Gazzard. “I’m a great believer that people who get the Nobel Prize have simple answers to complicated problems, not complicated answers that nobody understands.”

All photos of IAS 2007 Conference courtesy of International AIDS Society